The site of estradiol sensitization of the gonadotrope is prior to calcium mobilization.
In primary pituitary cell cultures prepared from ovariectomized rats, estradiol-17B (E2) sensitizes gonadotropes to stimulation of luteinizing hormone (LH) release by gonadotropin releasing hormone (GnRH). The calcium ionophore A23187, which stimulates LH release from the cells by Ca2+ mobilization at a post-receptor locus, and veratridine, which stimulates LH release by activation of endogenous ion channels, were used to localize the site of E2 action. Cells cultured in medium which was charcoal stripped (to remove steroids) or which contained 10(-8) M added E2 responded equally well to the ionophore and equally well to veratridine, indicating that the molecular locus of E2 action precedes Ca2+ mobilization. This type of analysis can be used to locate the site of action of compounds which alter the responsiveness of the pituitary to GnRH.
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002369:Castration; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014701:Veratridine / Q000494:pharmacology
D007987:Gonadotropin-Releasing Hormone; D000001:Calcimycin; D004958:Estradiol; D014701:Veratridine; D007986:Luteinizing Hormone; D002118:Calcium